NPASS Compound

Natural Product: NPC37074

Natural Product ID	NPC37074
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-Hydroxy-3-Methoxyphenyl Beta-D-Glucopyranosyl-(1->6)-Beta-D-Glucopyranoside
IUPAC Name	(2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(4-hydroxy-3-methoxyphenoxy)oxan-2-yl]methoxy]oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL550375
PubChem CID	42638297
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0004165] Phenolic glycosides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 60 62 0 0 0 0 0 0 0 0999 V2000 4.3700 2.3195 -2.0179 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2425 2.6215 -0.9592 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9699 1.7138 0.2324 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6689 1.9217 0.6247 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1436 0.8916 1.3970 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4487 -0.0376 0.6288 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1143 -0.0696 0.9982 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3190 -1.0711 0.1845 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9619 -1.0353 0.6088 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9419 -1.5326 -0.1776 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9221 -0.5473 -0.3678 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2355 -0.5800 0.0009 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8780 -1.5962 0.6421 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2165 -1.5096 0.9627 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9060 -0.3861 0.6306 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2969 0.6637 -0.0170 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9817 0.5620 -0.3243 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0849 1.7689 -0.3141 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5508 2.8922 -0.9754 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2632 -0.3094 0.9607 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5199 -2.0226 -1.5298 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6336 -0.9285 -2.1367 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5744 -0.8599 -1.2599 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5009 -1.8024 -1.7665 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3207 0.2782 -2.2328 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7889 -3.1853 -1.4918 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2188 0.1404 2.1485 C 0 0 1 0 0 0 0 0 0 0 0 0 5.0770 -0.5572 1.1160 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1355 0.2767 -0.1694 C 0 0 2 0 0 0 0 0 0 0 0 0 6.3094 0.0440 -0.8675 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4234 -1.7474 0.7674 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9383 0.9375 3.0022 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5308 3.0195 -2.7010 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3049 2.5467 -1.2588 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0415 3.6809 -0.6996 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7226 1.9814 1.0037 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4291 1.3580 2.1039 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9696 -0.3622 2.0705 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6512 0.9471 0.9109 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7473 -2.0813 0.4577 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4100 -2.3886 0.3423 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3209 -2.4923 0.9050 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7055 -2.3355 1.4749 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5090 1.4086 -0.8417 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2068 3.7625 -0.7626 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4741 2.7032 -2.0566 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5478 3.1458 -0.5863 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8067 -1.1457 0.8971 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4205 -2.1332 -2.1587 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3565 -1.2475 -3.1461 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0834 0.1325 -1.4129 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5925 -2.5788 -1.1574 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9677 0.9274 -1.5721 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0028 -3.7004 -0.6931 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7118 -0.6463 2.7436 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0948 -0.7489 1.4542 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2683 0.0177 -0.8378 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8560 -0.5731 -0.3351 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2347 -2.2842 1.5849 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5374 1.8333 3.1163 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 15 20 1 0 10 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 21 26 1 0 5 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 28 31 1 0 27 32 1 0 29 3 1 0 23 8 1 0 17 12 1 0 1 33 1 0 2 34 1 0 2 35 1 0 3 36 1 1 5 37 1 1 7 38 1 0 7 39 1 0 8 40 1 1 10 41 1 1 13 42 1 0 14 43 1 0 17 44 1 0 19 45 1 0 19 46 1 0 19 47 1 0 20 48 1 0 21 49 1 6 22 50 1 6 23 51 1 1 24 52 1 0 25 53 1 0 26 54 1 0 27 55 1 1 28 56 1 1 29 57 1 6 30 58 1 0 31 59 1 0 32 60 1 0 M END

Standard InCHIKey	CRFYIYVQFRJDLY-SKYGPZSASA-N
Standard InCHI	InChI=1S/C19H28O13/c1-28-9-4-7(2-3-8(9)21)30-19-17(27)15(25)13(23)11(32-19)6-29-18-16(26)14(24)12(22)10(5-20)31-18/h2-4,10-27H,5-6H2,1H3/t10-,11-,12-,13-,14+,15+,16-,17-,18-,19-/m1/s1
SMILES	OC[C@H]1O[C@@H](OC[C@H]2O[C@@H](Oc3ccc(c(c3)OC)O)[C@@H]([C@H]([C@@H]2O)O)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	464.15	Volume:	417.874 ? Van der Waals volume.
Dense:	1.111	LogP:	-0.898 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.171 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.031 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	18.0
TPSA:	207.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	3.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.196	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.265	Fsp³:	0.684
MCE-18:	79.75 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.463	Fluc inhibitor:	0.141 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.115 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.057 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.187	Promiscuous compounds:	0.265

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.497	MDCK Permeability:	-5.103
Pgp-inhibitor:	0.0	Pgp-substrate:	0.386
PAMPA:	0.985 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.981
20% Bioavailability (F20%):	0.265	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.1
Plasma Protein Binding (PPB):	51.4%	Volume Distribution (VD):	-0.515
Fu:	49.263% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.043
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.152
HLM stability:	0.005 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

1.356

Half-life (T1/2):

4.449

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.057
Human Hepatotoxicity (H-HT):	0.521	Drug-induced Liver Injury (DILI):	0.758
AMES Toxicity:	0.945	Rat Oral Acute Toxicity:	0.004
Maximum Recommended Daily Dose:	0.003	Skin Sensitization:	0.998
Carcinogencity:	0.089	Eye Corrosion:	0.0
Eye Irritation:	0.094	Respiratory Toxicity:	0.002
Drug-induced Neurotoxicity:	0.004	Ototoxicity:	0.984
Hematotoxicity:	0.258	Drug-induced Nephrotoxicity:	0.798
Genotoxicity:	0.07	RPMI-8226 Immunitoxicity:	0.149
A549 Cytotoxicity:	0.322	Hek293 Cytotoxicity:	0.174
BCF:	0.305 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	2.273 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.706 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.97 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33268	wheat	n.a.	n.a.	n.a.	wheat germ	n.a.	n.a.	PMID[19284743]
NPO33268	wheat	n.a.	n.a.	n.a.	wheat bran	n.a.	n.a.	PMID[21658963]
NPO33268	wheat	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Activity	1

Activity Type	# Activity
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.94	n.a.	PMID[19284743]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC37074 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	17271
0.1-0.2	27412
0.2-0.3	3575
0.3-0.4	1160
0.4-0.5	381
0.5-0.6	42
0.6-0.7	3
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9818	High Similarity	NPC287780
0.9818	High Similarity	NPC60982
0.7931	Intermediate Similarity	NPC189589
0.7797	Intermediate Similarity	NPC208769
0.7636	Intermediate Similarity	NPC221090
0.7458	Intermediate Similarity	NPC57751
0.6769	Remote Similarity	NPC60756
0.6515	Remote Similarity	NPC87696
0.6324	Remote Similarity	NPC25389
0.597	Remote Similarity	NPC469622
0.5763	Remote Similarity	NPC192810
0.5733	Remote Similarity	NPC5786
0.5663	Remote Similarity	NPC102028
0.5625	Remote Similarity	NPC46958
0.5526	Remote Similarity	NPC168358
0.5507	Remote Similarity	NPC298845
0.5432	Remote Similarity	NPC61791
0.5424	Remote Similarity	NPC142319
0.5397	Remote Similarity	NPC192229
0.5375	Remote Similarity	NPC476869
0.5366	Remote Similarity	NPC476865
0.5309	Remote Similarity	NPC476868
0.5294	Remote Similarity	NPC164047
0.5294	Remote Similarity	NPC470452
0.5294	Remote Similarity	NPC470453
0.5294	Remote Similarity	NPC198487
0.5294	Remote Similarity	NPC63105
0.5278	Remote Similarity	NPC469621
0.5275	Remote Similarity	NPC484980
0.5263	Remote Similarity	NPC3293
0.5246	Remote Similarity	NPC153149
0.5233	Remote Similarity	NPC213052
0.5217	Remote Similarity	NPC473045
0.5217	Remote Similarity	NPC171533
0.519	Remote Similarity	NPC229687
0.5172	Remote Similarity	NPC488073
0.5161	Remote Similarity	NPC25817
0.5161	Remote Similarity	NPC9248
0.5156	Remote Similarity	NPC145900
0.5143	Remote Similarity	NPC307110
0.5132	Remote Similarity	NPC34965
0.5132	Remote Similarity	NPC311803
0.5125	Remote Similarity	NPC476867
0.5082	Remote Similarity	NPC484157
0.5075	Remote Similarity	NPC205054
0.507	Remote Similarity	NPC278961
0.507	Remote Similarity	NPC113680
0.5065	Remote Similarity	NPC602810
0.5062	Remote Similarity	NPC476864
0.5062	Remote Similarity	NPC600240
0.5062	Remote Similarity	NPC609745

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC37074 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5374
0.1-0.2	3651
0.2-0.3	101
0.3-0.4	18
0.4-0.5	6
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data